VEGF is necessary for exercise-induced adult hippocampal neurogenesis

Eur J Neurosci. 2003 Nov;18(10):2803-12. doi: 10.1111/j.1460-9568.2003.03041.x.


Declining learning and memory function is associated with the attenuation of adult hippocampal neurogenesis. As in humans, chronic stress or depression in animals is accompanied by hippocampal dysfunction, and neurogenesis is correspondingly down regulated, in part, by the activity of the hypothalamic-pituitary-adrenal axis as well as glutamatergic and serotonergic networks. Antidepressants can reverse this effect over time but one of the most clinically effective moderators of stress or depression and robust stimulators of neurogenesis is simple voluntary physical exercise such as running. Curiously, running also elevates circulating stress hormone levels yet neurogenesis is doubled in running animals. In evaluating the signalling that running provides to the central nervous system in mice, we have found that peripheral vascular endothelial growth factor (VEGF) is necessary for the effects of running on adult hippocampal neurogenesis. Peripheral blockade of VEGF abolished running-induced neurogenesis but had no detectable effect on baseline neurogenesis in non-running animals. These data suggest that VEGF is an important element of a 'somatic regulator' of adult neurogenesis and that these somatic signalling networks can function independently of the central regulatory networks that are typically considered in the context of hippocampal neurogenesis.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Behavior, Animal
  • Blotting, Northern
  • Bromodeoxyuridine / pharmacokinetics
  • Cell Count
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / pharmacology
  • Enzyme-Linked Immunosorbent Assay
  • Extracellular Matrix Proteins / pharmacology
  • Genistein / pharmacology
  • Hippocampus / cytology
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Hippocampus / physiology*
  • Immunohistochemistry
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Confocal
  • Mitotic Index / methods
  • Myosin Heavy Chains
  • Neurons / drug effects
  • Neurons / physiology*
  • Neuropilins / metabolism
  • Nonmuscle Myosin Type IIB
  • Physical Conditioning, Animal / physiology*
  • Rats
  • Rats, Inbred F344
  • Reverse Transcriptase Polymerase Chain Reaction
  • Running
  • Stem Cells / metabolism
  • Tubulin / metabolism
  • Vascular Endothelial Growth Factor A / immunology
  • Vascular Endothelial Growth Factor A / physiology*
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism


  • Enzyme Inhibitors
  • Extracellular Matrix Proteins
  • Neuropilins
  • Tubulin
  • Vascular Endothelial Growth Factor A
  • Genistein
  • Vascular Endothelial Growth Factor Receptor-2
  • Nonmuscle Myosin Type IIB
  • nonmuscle myosin type IIB heavy chain
  • Myosin Heavy Chains
  • Bromodeoxyuridine